Breaking Down Analytical Performance Studies under IVDR: Methodologies and Best Practices
Read the latest blog from Abingdon Analytical Director, Candice Vendettuoli, who will be attending the upcoming Clinical Innovations EXPO in Nottingham on 15 May 2025. In this blog Candice provides a detailed overview on analytical performance studies under IVDR, a key part of your regulatory plan, and outlines some thoughts on best practice.
Introduction
The In Vitro Diagnostic Regulation (IVDR) has fundamentally transformed how IVD manufacturers demonstrate the performance of their devices. At the heart of this regulatory framework lies the performance evaluation process, with analytical performance studies serving as a critical cornerstone.
As a fully integrated CDMO and regulatory service provider specialising in IVDR compliance, we've guided numerous manufacturers through the complexities of analytical performance studies. This blog aims to demystify these studies, outlining key methodologies and sharing best practices based on our extensive experience.
Performance Evaluation under IVDR
The IVDR requires manufacturers to establish and document evidence that demonstrates their device achieves its intended purpose. This performance evaluation consists of three interconnected elements:
- Scientific Validity: Evidence establishing the association between an analyte and a clinical condition
- Analytical Performance: How well the device performs its intended technical function
- Clinical Performance: How well the device performs in achieving its clinical claims
This blog focuses primarily on the analytical performance component, while recognising its crucial links to the other elements.
What Are Analytical Performance Studies?
Analytical performance studies assess how well an IVD device performs its intended technical function. These studies evaluate the device's ability to correctly detect or measure a particular analyte, independent of any clinical considerations.
Under IVDR, analytical performance studies must address several key parameters (many of which align with FDA expectations for US market access):
- Analytical sensitivity: The ability to detect the presence of a target marker
- Analytical specificity: The ability to recognise only the target marker
- Trueness: The closeness of agreement between the average value from a large series of measurements and an accepted reference value
- Precision: The closeness of agreement between independent test results under stipulated conditions
- Limit of detection (LoD): The lowest amount of analyte that can be reliably detected
- Limit of quantitation (LoQ): The lowest amount of analyte that can be reliably measured
- Measuring range: The range within which the IVD demonstrates suitable analytical performance
- Linearity: The ability to provide results proportional to the concentration of analyte
- Cut-off value: The threshold value that determines positive from negative results
Common Challenges and How to Address Them
1. Reference Material and Standards
Challenge: Lack of suitable reference materials or standards for novel biomarkers.
Solution: Develop and validate in-house reference materials with thorough characterisation. Document the rationale and approach used for homemade reference materials in the technical documentation. Consider FDA or internationally recognised standards when available.
2. Matrix Effects
Challenge: Sample matrix variations affecting analytical performance.
Solution: Evaluate performance across different matrices relevant to the intended use. Consider lot-to-lot variation of collection devices or anticoagulants if applicable. Both FDA and IVDR expect robust matrix effect studies.
3. Statistical Analysis Complexity
Challenge: Choosing appropriate statistical methods for data analysis.
Solution: Develop a statistical analysis plan before study initiation. Consult with biostatisticians for complex assays or innovative statistical approaches. Both FDA and European regulators accept similar statistical methodologies.
4. Protocol Design
Challenge: Designing comprehensive protocols that address all required parameters.
Solution: Create a master validation plan that outlines the entire analytical performance assessment approach. Use risk analysis to prioritise critical performance parameters.
Documentation Requirements for IVDR Performance Evaluation
IVDR places significant emphasis on robust documentation throughout the performance evaluation process. For analytical performance studies specifically, key documentation elements include:
- Study protocols with pre-defined acceptance criteria
- Detailed raw data from all experiments
- Statistical analysis methods and results
- Clear conclusions regarding performance claims
- Discussion of limitations and potential impacts on clinical performance
This documentation must be organised to facilitate Notified Body review, with clear cross-referencing to requirements in IVDR Annex I and Annex II. Your documentation strategy should demonstrate how analytical performance evidence connects to scientific validity and clinical performance within your overall performance evaluation.
For manufacturers also targeting FDA submission, this documentation approach largely aligns with FDA expectations, though you may need to adjust the presentation format to match FDA guidance documents.
Best Practices for IVDR Performance Evaluation: Focus on Analytical Studies
Based on our experience supporting manufacturers through IVDR transitions, we recommend these best practices for analytical performance studies within your broader performance evaluation strategy:
- Start with a comprehensive risk analysis to identify critical performance parameters
- Design studies based on intended use and target population characteristics as defined in your performance evaluation plan
- Follow established guidelines (CLSI, ISO, etc.) to strengthen your technical documentation
- Use real-world samples that represent the intended use population
- Consider the entire measurement system, not just the analytical component
- Document all deviations from protocols and their impact on results
- Implement a staged approach to quickly identify major issues before comprehensive testing
- Maintain sample integrity through appropriate storage and handling
- Challenge the system with edge cases and worst-case scenarios
- Link analytical performance to clinical performance and overall benefit-risk assessment
- Plan for post-market performance follow-up as required by IVDR
- Consider global requirements early if FDA submission is also planned, to design studies that satisfy both regulatory frameworks efficiently
Conclusion
Performance evaluation under IVDR represents a comprehensive approach to demonstrating device safety and effectiveness, with analytical performance studies serving as a critical foundation. A systematic, thorough approach to these studies not only ensures IVDR compliance but also leads to better products that healthcare professionals can trust.
At Abingdon Analytical Ltd, we've developed specialised expertise in designing, conducting, and documenting analytical performance studies that meet IVDR requirements while minimising unnecessary testing. By following the methodologies and best practices outlined in this blog, manufacturers can navigate the analytical performance requirements of IVDR with confidence.
Abingdon Analytical is part of the Abingdon Health group. Abingdon Health’s team has over 20 years' experience in the lateral flow market, and is a knowledge leader in the development, scale-up, transfer, manufacturing and regulatory approval of lateral flow products across a range of sectors. If you require Analytical Performance Studies for your product, get in touch with Abingdon Analytical’s highly experienced team to explore how we can accelerate your route to market
